ABSTRACT: Non-Human Primate Core?Core 3 Mother to child transmission (MTCT) of HIV-1 continues to occur at an alarming rate of over a quarter million infant infections annually, despite the global scale-up of antiretroviral (ARV)-based prophylaxis during pregnancy and breastfeeding. The inability of ARV-based interventions, alone, to eliminate pediatric HIV-1 infections is due to several challenges, including: ARV access/adherence, acute infection of mothers, and the development of drug resistant virus strains. Thus, elimination of pediatric HIV-1 depends on the development of alternate strategies to interrupt MTCT. Strategies involving combined maternal and infant immune-based interventions have been effective against other neonatal pathogens, including hepatitis B and tetanus. In the case of HIV/SIV, previous maternal-infant non-human primate vaccine studies from our team members have achieved both partial protection of infants against oral SIV infection and robust, functional neutralizing maternal antibody responses in breast milk. Extending this work, the Non-Human Primate Core of this Program Project grant will test the hypothesis that infant HIV-1 acquisition via breastfeeding can be reduced by an approach combining maternal immunization and active immunization of the infant in the rhesus macaque model of postnatal HIV-1 transmission. Core 3, the Non-Human Primate (NHP) Core is an integral component of the overall HIVRAD program and provides direct support to the Projects by coordinating and implementing all the NHP experiments. The NHP Core will support Project 1, ?Development of a maternal vaccine to passively-immunize infants against clade C HIV-1 infection? (P.I. Dr. S. Permar, Duke University) aimed at studying the impact of maternal immunization, and Project 2 ?Development of a pediatric vaccine to protect infants against clade C HIV-1 infection? (Dr. K. Abel, Univ. of North Carolina, Chapel Hill), aimed at studying the effects of infant vaccination and the impact of combined maternal/infant immunization against oral SHIV transmission. Specifically, Core 3 will directly test in the NHP model whether vaccination of pregnant macaques and their infants with a nonreplicating MVA and/or DNA prime and combined systemic and mucosal transmitted/founder Envelope protein boost can reduce virus acquisition in a neonatal monkey oral low dose Simian-Human Immunodeficiency Virus (SHIV) challenge model developed by this Core. This work will be performed in settings that mimic both acute maternal infection and chronic, ARV-treated maternal infection. Together, the data obtained in the proposed NHP studies will provide understanding of the efficacy and protective mechanisms of combined maternal and infant immunization - information that is crucial to the design of effective maternal and infant HIV-1 vaccines and necessary to end the pediatric HIV-1 epidemic and achieve an HIV-1-free generation.